Interpretive Handbook

Test 83698 :
Wilson Disease Known Mutation, ATP7B DNA Sequencing

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Wilson disease (WD) is an autosomal recessive disorder that results from the body's inability to excrete excess copper. Typically, the liver releases excess copper into the bile. Individuals with WD lack the necessary enzyme that facilitates clearance of copper from the liver to bile. As a result, copper accumulates first in the liver and gradually in other organs. The brain, kidneys, bones, and corneas can also be affected. WD affects approximately 1 in 30,000 people worldwide, with a carrier frequency of approximately 1 in 90 individuals.


The primary clinical manifestations of WD are hepatic and neurologic. Hepatic disease can be quite variable, ranging from hepatomegaly or other nonspecific symptoms that mimic viral hepatitis to severe liver damage such as cirrhosis. Neurologic symptoms of WD can include poor fine-motor coordination, ataxia, and dysphagia. Psychiatric manifestations are reported in approximately 20% of individuals with WD. A characteristic ophthalmologic finding is the Kayser-Fleischer ring. Individuals with WD typically begin to show symptoms of liver dysfunction or neurologic disease in the first or second decade of life. If not treated, WD can cause liver failure, severe brain damage, and even death.


A variety of laboratory tests are recommended in the initial evaluation for WD. In approximately 95% of cases, serum ceruloplasmin is below normal. Additionally, patients with WD show decreased copper in serum, increased copper in urine, and significantly elevated copper on liver biopsy. While liver biopsy is not recommended as a first-tier screening test for WD, it can be useful to help interpret discrepant biochemical or molecular results. The other tests should be performed prior to sequence analysis of the ATP7B gene, the gene responsible for WD. More than 300 disease-causing mutations have been identified in the ATP7B gene. Most mutations are family-specific with the exception of the H1069Q mutation, which accounts for >50% of identified disease alleles in the Northern European Caucasian population.

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnostic confirmation of Wilson disease when familial mutations have been previously identified


Carrier testing of individuals when a mutation in the ATP7B gene has been identified in an affected family member.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing.


Analysis is performed for the familial mutations provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with Wilson disease.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Roberts EA, Schilsky ML: American Association for Study of Liver Diseases (AASLD): Diagnosis and treatment of Wilson disease: an update. Hepatology 2008;47(6):2089-2111

2. Mak CM, Lam CW: Diagnosis of Wilson's disease: a comprehensive review. Crit Rev Clin Lab Sci 2008;45(3):263-290